First Department of Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Immunobiology. 2012 Jan;217(1):54-60. doi: 10.1016/j.imbio.2011.08.002. Epub 2011 Sep 10.
Interleukin (IL)-17A is a cytokine involved in neutrophilic inflammation but the role of IL-17A in anti-tumor immunity is controversial because both pro- and anti-tumor activities of IL-17A have been reported. We hypothesized that constitutive expression of IL-17A in intestinal environment modifies tumor growth. To address the issue, mice were inoculated into subserosa of cecum (i.c.) with murine EL4 lymphoma expressing a model tumor antigen, and tumor growth was monitored. IL-17A-producing cells were detected both in tumor mass and in normal intestinal tissue of i.c. tumor-bearing wild type mice. Tumor size in the wild-type mice was significantly higher than that in the cecum of IL-17A gene-knockout mice. Furthermore, anti-IL-17A monoclonal antibody treatment of wild-type mice resulted in decreased tumor size in the cecum. Model tumor-antigen-specific interferon-γ production was not modified in draining mesenteric lymph node cells in the absence or after neutralization of IL-17A. All the results suggest that constitutive expression of IL-17A in intestine enhances tumor growth, and anti-IL-17A antibody treatment is a candidate of a new anti-tumor immunotherapy against intestinal tumors.
白细胞介素(IL)-17A 是一种参与中性粒细胞炎症的细胞因子,但 IL-17A 在抗肿瘤免疫中的作用存在争议,因为已经报道了 IL-17A 的促肿瘤和抗肿瘤活性。我们假设 IL-17A 在肠道环境中的组成性表达会改变肿瘤的生长。为了解决这个问题,将表达模型肿瘤抗原的鼠 EL4 淋巴瘤接种到盲肠(i.c.)的浆膜下,监测肿瘤生长。在 i.c.荷瘤野生型小鼠的肿瘤块和正常肠道组织中均检测到产生 IL-17A 的细胞。野生型小鼠的肿瘤大小明显高于 IL-17A 基因敲除小鼠的盲肠。此外,抗 IL-17A 单克隆抗体治疗野生型小鼠导致盲肠肿瘤体积减小。在缺乏或中和 IL-17A 后,引流肠系膜淋巴结细胞中模型肿瘤抗原特异性干扰素-γ 的产生没有改变。所有结果表明,肠道中 IL-17A 的组成性表达增强了肿瘤的生长,抗 IL-17A 抗体治疗是针对肠道肿瘤的新型抗肿瘤免疫治疗的候选药物。